Although the pathways for the biotransformation of fatty acids in liver endoplasmic reticulum are known, the enzymatic components of each pathway remain to be elucidated. At present the components of only one pathway, the delta 9 desaturation, have been established. Little or nothing is known about the constituents of the delta 5 and delta 6 desaturation and the chain elongation systems. It is the purpose of this proposed research to determine whether NADPH cytochrome c reductase, NADH cytochrome b5 reductase and cytochrome b5 are components of these biotransformation pathways. These enzymes will be "selectively" removed from the microsomal membrane, followed by determination of delta 5, delta 6 desaturase and chain elongation activity in these treated microsomes. The two reductases and the hemoprotein will be purified and will be used to monitor the solubilization and partial purification of both the delta 5 and delta 6 desaturases and the elongase complex. Antibodies to cytochrome b5 and NADPH cytochrome c reductase will be prepared from rabbit antiserum and their effect on the fatty acid biotransformation pathway will be measured. Reconstitution of the desaturase and elongation pathways will be attempted by combining the purified fractions. The importance of the elucidation of these pathways lies in the points of control or regulation, e.g., hormones like, insulin, glucagon, epinephrine and cAMP as well as diet (high carbohydrate, low protein, fasting) have profound effects on these biotransformation pathways. Hence, the relative activity of these pathways may play an important role in such disease states as atherosclerosis, ischemic heart disease, platelet dysfunction.